Understanding Neurotransmitters and Receptors is important due to the frequent use of psychotropic medications in psychiatry.
The dopamine, muscarinic, adrenergic, serotonin, opiate, and histamine receptors are all evolutionarily related to a common ancestor.
Dopamine | Serotonin | Acetylcholine | Norepinephrine | GABA | |
---|---|---|---|---|---|
Alzheimer's disease | - | - | ↓ | - | - |
Anxiety | - | ↓ | - | ↑ | ↓ |
Schizophrenia | ↑ (excess dopamine causes positive symptoms and psychosis) | - | - | - | - |
Depression | ↓ | ↓ | - | ↓ | - |
Huntington's disease | ↑ | - | ↓ | - | ↓ |
Parkinson's disease | ↓ (destruction of dopamine-producing substantia nigra) | ↓ | ↑ (cholinergic excess causes Parkinsonism) | - | - |
Neurotransmitters can be inhibitory (which reduces neuronal excitability), or be excitatory (which increases neuronal excitability). Inhibitory and excitatory action will decrease or increase, respectively, the likelihood that a neuron will fire an action potential.
Serotonin Receptor | Neurotransmitter | Receptory Type | Agonist | Partial Agonist | Antagonist |
---|---|---|---|---|---|
5-HT1 | Serotonin | G-protein coupled | • Mirtazapine (antidepressant effect) | - | Unknown downstream effects |
5-HT1A | Serotonin | G-protein coupled | Buspirone (anti-anxiety effects) | Anxiolytic (buspirone); booster of antidepressant action (aripiprazole) | - |
5-HT2A | Serotonin | G-protein coupled | Sexual dysfunction, insomnia, anxiety (SSRIs) | - | • Possible mood stabilizing and antidepressant actions in bipolar disorder (atypical antipsychotics) • Reduction of sexual dysfunction (trazodone, aripiprazole, cyproheptadine) • Reducing motor side effects from serotonin syndrome (cyproheptadine) • Mirtazapine (antidepressant effect) |
5-HT2C | Serotonin | G-protein coupled | Sexual dysfunction (SSRIs) | - | • Mirtazapine (antidepressant effect) |
5-HT3 | Serotonin | Ligand-gated ion channel (the only serotonin receptor one!) | • Not involved in psychiatric symptoms • These receptors do one thing mainly, and they do it well: when they stimulated (i.e. - targeted by an agonist) they make you really nauseous - if patients report nausea on an SSRI, this is why! | - | • Anti-nausea (mirtazapine,olanzapine, and ondansetron are all 5-HT3 antagonists) • Used in cancer populations for chemotherapy-related nausea |
5-HT4 | Serotonin | G-protein coupled | Increased GI motility, peristalsis, increase gastric emptying | - | - |
Dopamine Receptor | Neurotransmitter | Receptor Type | Agonist | Partial Agonist | Antagonist |
---|---|---|---|---|---|
D2 | Dopamine | G-protein coupled | L-dopa | Aripiprazole (partial agonist) creates an antipsychotic effect. | Typical and atypical antipsychotics create an antipsychotic effect. |
Receptor | Neurotransmitter | Receptor Type | Location | Function | Agonist | Partial Agonist | Antagonist |
---|---|---|---|---|---|---|---|
M1 | Acetylcholine | G-protein receptor | Central nervous system | Involved in perception, attention, and cognition. | Experimental drugs only | - | Many antipsychotics, and antidepressants can cause the anticholinergic effects of memory disturbance, sedation, dry mouth, blurred vision, constipation, urinary retention. Delirium is also associated with the antagonism of post-synaptic M1 receptors. |
M2 | Acetylcholine | G-protein receptor | Brain, heart | Decreases heart rate below baseline normal sinus rhythm by slowing the speed of depolarization. | - | - | - |
M3 | Acetylcholine | G-protein receptor | Smooth muscles, salivary glands | Causes contraction of smooth muscle, including bronchoconstriction and bladder voiding. | - | - | - |
M4 | Acetylcholine | G-protein receptor | Brain, lungs, salivary glands | There is a possible role for M4 receptors in regulating salivary protein secretion. Agonism of M4 is thought to be involved in clozapine-induced sialorrhea. | - | - | - |
M5 | Acetylcholine | G-protein receptor | Smooth muscles, salivary glands | - | - | - | May contribute to metabolic syndrome (dyslipidemia and diabetes), from some atypical antipsychotics |
In the synaptic cleft, acetylcholine binds to M or N receptors. Once in the cleft, ACh has 3 fates:
Acetylcholine activity can be modulated with 3 different classes of drugs:
Adrenergic agonists include:
Adrenergic antagonists include:
Histamine Receptor Subtype | Neurotransmitter | Receptor Type | Function | Location | Agonists | Antagonists/Blocker |
---|---|---|---|---|---|---|
H1 | Histamine | G-protein | Allergic responses | Smooth muscle and endothelial cells | Hydroxyzine (inverse agonist - acts like an antagonist), Betahistine (H1 agonist) | • First-generation: Diphenhydramine • Second-generation: Loratadine, cetirizine Therapeutic effect for anxiety and insomnia; side effect of sedation and weight gain Also trazodone |
H2 | Histamine | G-protein | Stimulation of gastric acid | Gastric parietal cells | Betazole (H2 agonist - stimulates gastric secretions) | Ranitidine |
H3 | Histamine | G-protein | Release of neurotransmitters including histamine, acetylcholine, dopamine, norepinephrine, and others involved in cognition | Presynaptic receptors in central nervous system | None | Betahistine |
H4 | Histamine | G-protein | Inflammatory responses | Hematopoietic cells such as eosinophils, mast cells, neutrophils, and dendritic cells | None | None |